This research program has been designed to examine the mechanisms by which N. gonorrhoeae causes disease. The Principal Investigator and colleagues have previously designed an experimental model which employs human fallopian tube pieces in organ culture for quantitation of rate of damage to genital mucosa by gonococci. This model will be used to test various gonococcal strains that differ in one or more characteristics to determine if those characteristics are associated with increased virulence. Efforts will be made to detect the presence of a toxin produced by gonococci and to determine its effects on mucosal cells. Studies of the mechanisms of interaction between gonococci and the fallopian tube mucosa will focus on the attachment phase and on the apparent ingestion of gonococci by mucosal cells. The possible elaboration of capsular material by gonococci in organ culture and in various media will be assessed by light and electron microscopic techniques. The formation of wall defective variants of gonococci and their persistence as L-phase variants in fallopian tubes in organ culture will also be studied. A better understanding of the pathogenic mechanisms in gonococcal infections and identification of virulence factors is critical in the effort to immunize against these factors or otherwise interfere with their role in the disease process.